Dry Eye Syndromes
Conditions
Brief summary
Carboxymethylcellulose (CMC), a common component in artificial tears, has been shown to modify the gut microbiome. The study is examining its effects on the eye microbiome, which may have implications on ocular disease and artificial tear choice. The study will administer artificial tears containing CMC to the treatment group and artificial tears without CMC to the control group. Surveys and conjunctival swabs will be collected before and after treatment for bacterial genome sequencing and analyzed by R statistical packages.
Interventions
DRUGCarboxymethylcellulose (CMC) Artificial Tears
A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group.
DRUGPreservative-free, CMC-free Artificial Tears (control)
A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group.
Sponsors
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults above age 18 of either sex who can self-administer artificial tears and return for follow-up at the UF Oaks Eye Clinic.
Exclusion criteria
* Individuals with active eye infections or have prosthetic eyes. * Are immunocompromised, or are diagnosed with autoimmune diseases or malignant neoplasms about the eye. * Individuals who take immunomodulatory therapy, steroids, antibiotics, medicated eyedrops, or are already using CMC eyedrops within 1 week of the study will also be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Species Richness | Assessed at day 1 and day 7, day 7 reported. | Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Faith's phylogenetic diversity was used as a measure of species richness, calculated as the sum of all phylogenetic tree branch lengths using the QIIME2 faith\_pd plugin. The units for this measure are the number of nucleotide substitutions (phylogenetic distance, i.e. length) per branch, which is a scale measure from zero to infinity. Zero indicates a completely homogenous sample, and higher scores indicate greater species richness. |
| Species Diversity | Assessed at day 1 and day 7, day 7 reported. | Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold. Shannon's diversity index was used as a measure of species diversity, calculated as the sum of -p/ln(p), where p is the proportion of the sample made up of each OTU using the QIIME2 shannon\_pd plugin. This measure is a unitless scale proportion ranging from zero to infinity. Zero indicates a completely homogenous sample, and higher scores indicate greater species diversity. |
| Beta Diversity (Unweighted UniFrac) | Assessed at day 1 and day 7, difference between day 1 and day 7 reported. | Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Unweighted UniFrac distances were calculated as the number of shared nucleotide substitutions between two samples divided by the number of shared nucleotide substitutions among all samples using the QIIME2 unifrac plugin. The unweighted UniFrac is a unitless scale proportion ranging from zero to one. Greater UniFrac distances indicate greater beta diversity. |
| Beta Diversity (Weighted UniFrac) | Assessed at day 1 and day 7, difference between day 1 and day 7 reported. | Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Weighted UniFrac distances were calculated as the number of shared nucleotide substitutions between two samples divided by the number of shared nucleotide substitutions among all samples using the QIIME2 unifrac plugin, with samples weighted by abundance of species. The weighted UniFrac (weighted by number of duplicate OTUs) is a unitless scale proportion ranging from zero to infinity. Greater UniFrac distances indicate greater beta diversity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Surface Disease Index Score | Assessed at day 1 and day 7, difference between day 1 and day 7 reported. | The Ocular Surface Disease Index (OSDI) is a 12-item scale for the assessment of symptoms related to dry eye disease and their effect on vision. Participants conducted a survey before and after intervention, and the difference will be used as the outcome measure. The OSDI ranges from 0 to 48, and a higher score indicates greater ocular surface dryness. If reporting the difference, a more negative change in OSDI indicates greater improvement in dry eye symptoms. Pairwise Wilcoxon signed rank tests were used to compare changes in OSDI between intervention groups at a two-tailed 95% confidence interval. |
| Artificial Tear Use | Assessed at day 7 | Patients will be asked 1 week after intervention how many times they administered eye drops each day. This measures compliance with intervention, ranging from zero drops per day to infinite drops per day. If a patient is perfectly compliant, the number of drops should be 3. Mann-U-Whitney tests were used to compare compliance between intervention groups at a two-tailed 95% confidence interval. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carboxymethylcellulose (CMC) Artificial Tears Refresh brand artificial tears containing 0.5% carboxymethylcellulose will be self-administered three times a day in each eye by the participants for 1 week in the experimental arm.
Carboxymethylcellulose (CMC) Artificial Tears: A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group. | 40 |
| Preservative-free, CMC-free Artificial Tears Systane brand artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be self-administered three times a day in each eye by the participants for 1 week in the control arm.
Preservative-free, CMC-free Artificial Tears (control): A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group. | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 9 |
Baseline characteristics
| Characteristic | Preservative-free, CMC-free Artificial Tears | Total | Carboxymethylcellulose (CMC) Artificial Tears |
|---|---|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 13.8 | 40.6 years STANDARD_DEVIATION 15.6 | 41.1 years STANDARD_DEVIATION 17.4 |
| Contact lens use | 10 Participants | 19 Participants | 9 Participants |
| Ocular surgery history | 10 Participants | 17 Participants | 7 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 40 Participants | 80 Participants | 40 Participants |
| Sex: Female, Male Female | 28 Participants | 55 Participants | 27 Participants |
| Sex: Female, Male Male | 12 Participants | 25 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 0 / 40 | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
Beta Diversity (Unweighted UniFrac)
Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Unweighted UniFrac distances were calculated as the number of shared nucleotide substitutions between two samples divided by the number of shared nucleotide substitutions among all samples using the QIIME2 unifrac plugin. The unweighted UniFrac is a unitless scale proportion ranging from zero to one. Greater UniFrac distances indicate greater beta diversity.
Time frame: Assessed at day 1 and day 7, difference between day 1 and day 7 reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboxymethylcellulose (CMC) Artificial Tears | Beta Diversity (Unweighted UniFrac) | 0.482 score on a scale |
| Preservative-free, CMC-free Artificial Tears | Beta Diversity (Unweighted UniFrac) | 0.529 score on a scale |
Comparison: Repeated measures Mann-U-Whitney tests were used to compare changes in weighted and unweighted UniFrac distances between intervention groups before and after intervention at a two-tailed 95% confidence interval.p-value: 0.227Repeated measures Mann-U-Whitney
Primary
Beta Diversity (Weighted UniFrac)
Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Weighted UniFrac distances were calculated as the number of shared nucleotide substitutions between two samples divided by the number of shared nucleotide substitutions among all samples using the QIIME2 unifrac plugin, with samples weighted by abundance of species. The weighted UniFrac (weighted by number of duplicate OTUs) is a unitless scale proportion ranging from zero to infinity. Greater UniFrac distances indicate greater beta diversity.
Time frame: Assessed at day 1 and day 7, difference between day 1 and day 7 reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboxymethylcellulose (CMC) Artificial Tears | Beta Diversity (Weighted UniFrac) | 0.584 score on a scale |
| Preservative-free, CMC-free Artificial Tears | Beta Diversity (Weighted UniFrac) | 0.593 score on a scale |
Primary
Species Diversity
Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold. Shannon's diversity index was used as a measure of species diversity, calculated as the sum of -p/ln(p), where p is the proportion of the sample made up of each OTU using the QIIME2 shannon\_pd plugin. This measure is a unitless scale proportion ranging from zero to infinity. Zero indicates a completely homogenous sample, and higher scores indicate greater species diversity.
Time frame: Assessed at day 1 and day 7, day 7 reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carboxymethylcellulose (CMC) Artificial Tears | Species Diversity | 3.9 score on a scale | Standard Deviation 1.1 |
| Preservative-free, CMC-free Artificial Tears | Species Diversity | 4.1 score on a scale | Standard Deviation 1.1 |
Comparison: ANOVA was used to compare mean Shannon's diversity indices before and after treatment for each intervention group at a two-tailed 95% confidence interval.p-value: 0.224ANOVA
Primary
Species Richness
Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Faith's phylogenetic diversity was used as a measure of species richness, calculated as the sum of all phylogenetic tree branch lengths using the QIIME2 faith\_pd plugin. The units for this measure are the number of nucleotide substitutions (phylogenetic distance, i.e. length) per branch, which is a scale measure from zero to infinity. Zero indicates a completely homogenous sample, and higher scores indicate greater species richness.
Time frame: Assessed at day 1 and day 7, day 7 reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carboxymethylcellulose (CMC) Artificial Tears | Species Richness | 11.0 units on a scale | Standard Deviation 2.1 |
| Preservative-free, CMC-free Artificial Tears | Species Richness | 11.1 units on a scale | Standard Deviation 3.3 |
p-value: 0.232ANOVA
Secondary
Artificial Tear Use
Patients will be asked 1 week after intervention how many times they administered eye drops each day. This measures compliance with intervention, ranging from zero drops per day to infinite drops per day. If a patient is perfectly compliant, the number of drops should be 3. Mann-U-Whitney tests were used to compare compliance between intervention groups at a two-tailed 95% confidence interval.
Time frame: Assessed at day 7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carboxymethylcellulose (CMC) Artificial Tears | Artificial Tear Use | 2.86 eyedrops per day | Standard Deviation 0.81 |
| Preservative-free, CMC-free Artificial Tears | Artificial Tear Use | 2.16 eyedrops per day | Standard Deviation 0.82 |
Secondary
Ocular Surface Disease Index Score
The Ocular Surface Disease Index (OSDI) is a 12-item scale for the assessment of symptoms related to dry eye disease and their effect on vision. Participants conducted a survey before and after intervention, and the difference will be used as the outcome measure. The OSDI ranges from 0 to 48, and a higher score indicates greater ocular surface dryness. If reporting the difference, a more negative change in OSDI indicates greater improvement in dry eye symptoms. Pairwise Wilcoxon signed rank tests were used to compare changes in OSDI between intervention groups at a two-tailed 95% confidence interval.
Time frame: Assessed at day 1 and day 7, difference between day 1 and day 7 reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboxymethylcellulose (CMC) Artificial Tears | Ocular Surface Disease Index Score | -1 score on a scale |
| Preservative-free, CMC-free Artificial Tears | Ocular Surface Disease Index Score | -2 score on a scale |